rs1902586

Variant names:

• chr15-51278656-G-A
• rs1902586
• NM_000103.4:c.-38-35706C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000103.4(CYP19A1):​c.-38-35706C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,176 control chromosomes in the GnomAD database, including 5,561 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (5561 hom., cov: 32)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 20 publications found

Genes affected

CYP19A1 (HGNC:2594): (cytochrome P450 family 19 subfamily A member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and catalyzes the last steps of estrogen biosynthesis. Mutations in this gene can result in either increased or decreased aromatase activity; the associated phenotypes suggest that estrogen functions both as a sex steroid hormone and in growth or differentiation. Alternative promoter use and alternative splicing results in multiple transcript variants that have different tissue specificities. [provided by RefSeq, Dec 2016]

MIR4713HG (HGNC:53124): (MIR4713 host gene)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.-38-35706C>T		intron_variant	Intron 1 of 9	ENST00000396402.6	NP_000094.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP19A1	ENST00000396402.6	c.-38-35706C>T		intron_variant	Intron 1 of 9	1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29134 AN: 152058 Hom.: 5514 Cov.: 32

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.0685

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.0808

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0468

Gnomad OTH AF: 0.139

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.192 AC: 29247 AN: 152176 Hom.: 5561 Cov.: 32 AF XY: 0.195 AC XY: 14489 AN XY: 74392

African (AFR) AF: 0.479 AC: 19896 AN: 41496

American (AMR) AF: 0.130 AC: 1994 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0685 AC: 238 AN: 3472

East Asian (EAS) AF: 0.305 AC: 1579 AN: 5178

South Asian (SAS) AF: 0.242 AC: 1167 AN: 4818

European-Finnish (FIN) AF: 0.0808 AC: 855 AN: 10586

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0467 AC: 3179 AN: 68016

Other (OTH) AF: 0.147 AC: 310 AN: 2112

Alfa AF: 0.0956 Hom.: 881

Bravo AF: 0.206

Asia WGS AF: 0.321 AC: 1116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.16
DANN	Benign	0.56
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1902586; hg19: chr15-51570853;